Dexmedetomidine and Delirium in Patients After Cardiac Surgery

Delirium Clinical Trial

Official title:

Impact of Dexmedetomidine on the Incidence of Postoperative Delirium in Patients After Cardiac Surgery: a Randomized, Double-blinded, and Placebo-controlled Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02267538
• Other study ID #: PekingUFH
• Status: Completed
• Phase: Phase 4
• First received: October 9, 2014
• Last updated: February 3, 2018
• Start date: November 2014
• Est. completion date: November 2015

Study information

• Verified date: February 2018
• Source: Peking University First Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Postoperative delirium (POD) is a frequently occurring complication after cardiac surgery. Its occurrence is associated with worse outcomes of patients, including increased morbidity, prolonged hospital stay, increased medical cost, and higher mortality. It is also associated with long-term cognitive decline and decreased quality of life. However, until recently, pharmacological interventions that can effectively prevent its occurrence are still limited. The purpose of this study is to investigate whether perioperative dexmedetomidine use can decrease the incidence of postoperative delirium in patients undergoing cardiac surgery.

Description:

Delirium is a state of global cerebral dysfunction manifested by acute disturbance of consciousness, attention, cognition and perception. It develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day. The reported incidences of delirium after cardiac surgery varied from 21% to 47%. The occurrence of postoperative delirium has significant harmful effects on patients' outcomes, including increased morbidity, prolonged hospital stay, increased medical cost, and higher mortality. Its occurrence is also associated with long-term cognitive decline and decreased quality of life.

The exact pathogenesis that lead to the occurrence of POD are still unclear, and possibly involves mechanisms such as inflammation, pain and sleep deprivation after surgery. Furthermore, it has been shown that anesthesia management might also have exerted some effects. Studies found that avoidance of unnecessary deep anesthesia (under the guidance of Bispectral Index monitoring) decreases the incidence of POD. Theoretically, measures that decreases the requirement of anesthetics while maintaining adequate depth of anesthesia and those that alleviates inflammation and improves postoperative analgesia as well as sleep quality will decrease the incidence of POD.

Dexmedetomidine is a highly selective alpha-2 adrenoreceptor agonists that provides anxiolysis, sedation and modest analgesia with minimal respiratory depression. Studies showed that, when used as an adjunctive anesthetics, dexmedetomidine significantly decreases the requirement of opioid analgesics and other sedatives during anesthesia. A recent study of our group found that continuous infusion of low-dose dexmedetomidine (0.2 ug/kg/h) during the first night after surgery significantly improved subjective sleep quality. Two randomized controlled trials found that, when compared with traditional sedatives (midazolam and propofol) and analgesics (such as morphine), use of dexmedetomidine in patients after cardiac surgery is associated with decreased risk of delirium. However, questions still exist as to whether dexmedetomidine prevent delirium or just does not increase its occurrence since traditional sedatives/analgesics themselves increases the risk of delirium. Furthermore, animal experiments showed that dexmedetomidine inhibits the degree of inflammation induced by endotoxins.

The investigators hypothesize that use of dexmedetomidine as an adjunctive agent during the perioperative period can decrease the incidence of postoperative delirium in patients undergoing cardiac surgery, possibly by decreasing the requirement of anesthetics during surgery, by ameliorating analgesia as well as sleep quality after surgery, and by alleviating the degree of perioperative inflammatory response.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 285
• Est. completion date: November 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 90 Years

Eligibility

Inclusion Criteria:

Patients of 60 years or older who are planning to receive cardiac surgery (CABG and/or valve replacement surgery)

Exclusion Criteria:

Patients will be excluded if they meet any of the following criteria:

1. Refuse to participate;

2. Preoperative history of schizophrenia, epilepsia, Parkinson syndrome, or severe dementia;

3. Inability to communicate in the preoperative period because of severe visual/auditory dysfunction or language barrier;

4. History of brain injury or neurosurgery;

5. Preoperative sick sinus syndrome, severe bradycardia (HR < 50 bpm), second-degree or above atrioventricular block without pacemaker;

6. Severe hepatic dysfunction (Child-Pugh class C);

7. Severe renal dysfunction (requirement of renal replacement therapy);

8. Other conditions that are considered unsuitable for participation.

Related Conditions & MeSH terms

• C.Surgical Procedure; Cardiac
• Delirium
• Postoperative Complications

Intervention

Drug:
• dexmedetomidine hydrochloride for injection
Before anesthesia, dexmedetomidine hydrochloride for injection (200 ug/2 ml) will be diluted with normal saline to 50 ml (final dexmedetomidine concentration 4 ug/ml). Before the induction of anesthesia, a loading dose will be administered by intravenous infusion at a rate of [0.9*kg] ml/h for 10 minutes (i.e., dexmedetomidine 0.6 µg/kg in 10 minutes), followed by continuous infusion at a rate of [0.1*kg] ml/h (i.e., dexmedetomidine at a rate of 0.4 µg /kg/h) until the end of surgery. At the end of surgery, the infusion rate will be decreased to [0.025*kg] ml/h (i.e., dexmedetomidine at a rate of 0.1 ug/kg/h) and continued until the end of mechanical ventilation after surgery.
• 0.9% sodium chloride for injection
Before anesthesia, 0.9% sodium chloride for injection 50 ml will be prepared. Before the induction of anesthesia, a loading dose will be administered by intravenous infusion at a rate of [0.9*kg] ml/h for 10 minutes, followed by continuous infusion at a rate of [0.1*kg] ml/h until the end of surgery. At the end of surgery, the infusion rate will be decreased to [0.025*kg] ml/h and continued until the end of mechanical ventilation after surgery.

Locations

Country	Name	City	State
China	Peking University First Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking University First Hospital	Chinese Academy of Medical Sciences, Fuwai Hospital

Country where clinical trial is conducted

China, 

References & Publications (48)

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* Note: There are 48 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pain Intensity	Pain intensity was assessed daily at 8 am during the first five days after surgery with the Numeric Rating Scale (NRS, 0 = no pain, 10 = the worst possible pain).	During the first five days after surgery
Other	Subjective Sleep Quality	Subjective sleep quality was assessed daily at 8 am during the first five days after surgery with the Numeric Rating Scale (NRS, 0 = best sleep, 10 = the worst possible sleep).	During the first five days after surgery
Other	Length of Stay in the Intensive Care Unit	Results was presented as median (95% confidence interval).	From end of surgery until discharge from Intensive Care Unit or 30 days after surgery
Other	Length of Stay in Hospital After Surgery	Results was presented as median (95% confidence interval).	From end of surgery until discharge from hospital or 30 days after surgery
Primary	Incidence of Postoperative Delirium	Delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) twice daily during the first five days after surgery.	During the first five days after surgery
Secondary	Cognitive Function	Cognitive function was assessed with the Mini Mental State Examination (MMSE) at baseline (the day before surgery) and on the sixth day after surgery, and with modified telephone interview for cognitive status (m-TICS) on the 30th day after surgery.; The introduction of MMSE scale has been explained in the baseline part in the result section.; The Telephone Interview for Cognitive Status-modified scale(m-TICS) is one of the most popular telephone interview-based screening instruments for mild cognitive impairment and dementia. It consists 11 items including wordlist memory, orientation, attention, repetition, conceptual knowledge and nonverbal praxis, which score ranges from 0 to 48, with higher scores indicating better cognitive function	on the sixth day after surgery, and on the 30th day after surgery
Secondary	Incidence of Non-delirium Complications After Surgery	Non-delirium complications was defined as any conditions other than delirium that occurred during the first 30 days after surgery and required therapeutic intervention.Complications listed here were not considered adverse events in this study.	Occurrence of non-delirium complications will be monitored until 30 days after surgery.

External Links

•   Confusion Assessment Method (CAM) training manual and coding guide were found in this web.
•   Different versions of Confusion Assessemnt Method for the Intensive Care Unit (CAM-ICU) and their validation papers were found in this web.